Genomic restriction fragment polymorphisms for the human EAlpha, EBeta, AAlpha, and ABeta genomic sequences, HLA-DR type, and two dimensional protein electrophoresis pattern for the EAlpha, EBeta, AAlpha, and ABeta polypeptide chains will be correlated for consanguineousmating derived homozygous typing cells of HLA-DR3 and DR4 serotypes, and for a wide variety of homozygous typing cells corresponding to the other established HLA-DR types. Similar analyses will be done on peripheral blood lymphocytes isolated from patients with insulin dependent diabetes mellitus who are HLA-DR3 positive; Graves' disease patients who are HLA-DR3 positive; and insulin dependent diabetes mellitus and rheumatoid arthritis patients who are HLA-DR4 positive. By a combination of restriction fragment polymorphism, serotyping, and two-dimensional protein electrophoresis it is hoped to develop methods for subdividing HLA-DR chromosomes identified by serotyping with HLA-DR alloantisera into subsets or haplotypes which predispose to specific autoimmune diseases. These studies should lead to a much more precise identification of genetic susceptibility to these diseases and to identification of the particular loci which are most important in disease predisposition.